PROJECT SUMMARY Patient Oriented Research (POR) that focuses on understanding disease mechanisms and classifying diseases based on biology is especially powerful in this era of genomics and informatics. By combining a firm understanding of the design and conduct of rigorous human studies with the growing toolkit of the molecular biologist and geneticist, modern patient-oriented physician-scientists have the potential to overcome age-old barriers to the development of targeted therapies in common and morbid respiratory diseases. The goal of this application is to effectively mentor young patient-oriented research scientists in translational POR in a way that integrates clinical research methods and innovative bench methods (applied to human samples) to advance precision medicine. My research career has been devoted to integrating clinical and bench research methods to ask clinically-relevant questions in human studies. These include: (1) applying molecular phenotyping to asthma and COPD to identify subgroups characterized by type 2 inflammation and (2) revisiting the basic clinical criteria for diagnosis of COPD to account for ?smokers with symptoms despite preserved pulmonary function?, a subgroup that is not captured in existing guidelines, and then studying the biology underlying this condition. The goal of this K24 grant application is to further augment my capabilities in POR and to provide mentoring to junior investigators in translational approaches to POR. Some of these mentees, especially my direct mentees, are already pursuing work at the interface of clinical and translational research. Others are primarily trained in traditional clinical research methods and have expressed a desire to gain bench experience with human samples. Finally, a smaller but important group consists of mentees trained in basic science who wish to learn the methods of POR to forge human relevance for their work. I believe all of these diverse approaches to translational POR are valuable. With the support of my Division, I am starting a ?Pulmonary Precision Medicine Core Laboratory? at UCSF which will provide scalable space and resources and a common area for didactics and informal research interactions all oriented towards translational POR. This K24 grant will protect my time and provide resources (some matched by Divisional resources) to ensure the success of this endeavor. This K24 grant application proposes three aims. The first two are scientific aims that reflect two overarching research areas and provide ample opportunity for mentees interested in POR in asthma and COPD. My third aim, which is organizational, describes my approach to developing this core training laboratory designed to mentor junior investigators who are interested in translational POR in a range of pulmonary diseases.